Researchers from Stanford Medicine have discovered a naturally occurring molecule that may provide an alternative to the weight loss drug semaglutide, commonly known by its brand name, Ozempic.
This new molecule, BRP, appears to suppress appetite and promote weight loss without some unpleasant side effects of semaglutide, including nausea and constipation.
Professor Katrin Svensson, who led the research, explained that while semaglutide targets receptors found in the brain as well as in the gut and pancreas, BRP seems to work more specifically within the hypothalamus, a part of the brain that regulates appetite and metabolism.
This distinction could mean a more focused approach to controlling weight and reducing body fat.
Natural peptide
Svensson has co-founded a company that plans to conduct clinical trials with BRP in humans soon. The findings, published on March 5 in the journal Nature, suggest that BRP could offer a promising new avenue for treating obesity.
The research group utilized artificial intelligence to sift through various prohormones — molecules that can be transformed into active peptides, or hormones, that regulate body functions.
By focusing on prohormone convertase 1/3, a protein known to be associated with obesity, the team was able to identify several peptides that could influence energy metabolism.
Traditional isolating peptides can be incredibly challenging due to the numerous natural byproducts generated during protein processing.
The researchers developed a computer algorithm called Peptide Predictor to address this issue. This tool helped them determine the cleavage sites of prohormones in human proteins, narrowing their search down to 373 candidates that produce biologically active peptides.
Once identified, the researchers screened 100 peptides for their effects on lab-grown neuronal cells. Their results showed that GLP-1, a peptide that semaglutide mimics, significantly increased the activity of these cells.
However, they also found that a smaller peptide derived from the prohormone BRINP2, named BRP, significantly outperformed GLP-1, boosting neuronal activity tenfold compared to the control group.
Weight loss without side effects
To further investigate BRP’s effects, the researchers conducted experiments on lean mice and minipigs, which are thought to reflect human metabolism better.
They discovered that an intramuscular injection of BRP before feeding could reduce food intake by up to 50% in both animal models within an hour.
Over 14 days, obese mice receiving daily BRP injections lost around 3 grams, mostly from fat, while control mice gained weight.
These studies also indicated no notable differences in activity levels, water consumption, or signs of discomfort among the treated animals, suggesting that BRP does not adversely impact other aspects of health.
Additionally, investigations into physiological changes showed that BRP activates unique metabolic and neuronal pathways distinct from those engaged by GLP-1.
The research team hopes to identify the cell-surface receptors that respond to BRP to gain further insights into how it works.
They are also exploring strategies for enhancing the duration of BRP’s effects, aiming for a more sustained impact on appetite and metabolism.
As interest in effective and safe weight loss solutions rises, the findings surrounding BRP present an intriguing possibility. If clinical trials demonstrate its safety and efficacy in humans, BRP could represent a valuable addition to the tools available for addressing obesity and metabolic disorders.